RESISTANCE OF BACTERIA 217 



medium, but rather owing to the fact that the gelatin does not permit the 

 diffusion of the products formed during bacteriophagy, products which 

 inhibit the action of the bacteriophage. 



If we repeat these experiments by spreading a drop of a secondary 

 culture over the surface of (a) a gelatin medium (bouillon containing 

 15 per cent gelatin), and (b) the same gelatin medium spread out in a 

 thin layer over a substratum of agar, we will find that after incubation 

 at 22°C. the gelatin is covered by a continuous bacterial layer composed 

 of a mixed culture — resistant bacteria-virulent bacteriophage cor- 

 puscles. Upon the thin layer of gelatin spread over the agar there will 

 be, either no colonies at all, or only isolated colonies, depending upon 

 the virulence of the bacteriophage. Here again, this result can be 

 explained only as a result of the concentration at the surface of the first 

 medium of products inhibiting the action of the bacteriophage. In the 

 second medium these products diffuse into the deep substratum. 



It seems to me that these experiments leave no doubt but that 

 products inhibiting the action of the bacteriophage are formed during 

 bacteriophagy, and that these products are, in the last analysis, the 

 cause of secondary cultures. 



What is the origin of these inhibiting substances? Certainly they 

 are not products resulting from the normal metabolism of the bacteria, 

 for bacteriophagy takes place normally in filtrates of old cultures. 

 This being true it must be that these substances are secreted by the 

 bacteria in their reaction to the bacteriophage. They are then true 

 bacterial immune substances. A bacteriophage is, indeed, most highly 

 virulent when it resists the action of these inhibiting substances. 



The degree of virulence of a bacteriophage corpuscle for a given 

 bacterium represents, therefore, two factors, one being an ability to 

 multiply at the expense of the substance of this bacterium, the other, 

 its power to resist the action of the inhibiting substances secreted by 

 the bacterium which is reacting to its action. 



10. THE RESISTANT BACTERIUM 



It is necessary first of all to point out the difference between a 

 resistance acquired to the action of the bacteriophage and the natural 

 resistance possessed by a bacterial strain. We are concerned here with 

 acquired resistance only. It may be stated, however, that the natural 

 resistance which occurs in a bacterium belonging to a heterogeneous 

 species is not characterized by any peculiar sign. Such a bacterium is 

 normal both morphologically and in its biological properties. As for 



